A time-of-flight type mass spectrometer (hereinafter called a “TOFMS”) typically introduces ions accelerated by an electric field into a flight space that does not have an electric field or a magnetic field, allowing the ions to fly freely, and then separates various ions by each mass/charge ratio m/z in accordance with the time of flight until the ions reach a detector. In order to enhance the mass resolution in the TOFMS, it is necessary to increase the flight distance, and known configurations for achieving this include, in addition to a linear configuration in which ions are simply allowed to fly linearly, a reflectron configuration in which ions are allowed to make a return flight using an electric field or a magnetic field and a multi-turn configuration in which ions are allowed to make a plurality of roughly identical closed orbits.
A matrix assisted laser desorption/ionization (MALDI) ion source based on the MALDI method is widely used as a TOFMS ion source. In the MALDI method, a sample is prepared, for example, by mixing a solution of a substance to be measured with a matrix solution, mixing a separate ionization auxiliary agent into the solution if necessary, applying the solution to a sample plate, and removing the solvent by drying or the like. A sample prepared in this way is in a state in which the substance to be measured is practically uniformly mixed with a large quantity of a matrix. When this sample is irradiated with a laser beam, the matrix absorbs the energy of the laser beam and converts the energy into thermal energy. At this time, part of the matrix is rapidly heated and vaporized together with the substance to be measured, and the substance to be measured is ionized in this process.
In a TOFMS using a MALDI ion source, various ions generated from the sample due to the aforementioned laser beam irradiation are extracted from the vicinity of the sample by the effect of the electric field, and these ions are accelerated and fed into the flight space. In order to achieve high mass resolution, it is necessary for the initial speeds of the same types of ions (having identical mass/charge ratios) to be aligned when the ions are introduced into the flight space. However, in a MALDI ion source, there is typically large variation in the initial energy of ions at the point when the ions are generated, which leads to large variation in the initial speed and diminishes the time convergence. Therefore, a technique called delayed extraction is widely used to avoid this problem (see Patent Literatures 1, 2, and the like).
FIG. 6 is a schematic view for explaining the ion extraction operation using delayed extraction. As illustrated in FIG. 6(a), a sample S in which a matrix is mixed is held on an electrically conductive sample plate 1, and the sample S is irradiated with a laser beam for ionization for a short period of time. Ions flying out of the sample S due to laser beam irradiation are extracted to the right in the drawing from the vicinity of the sample S and fed to a flight space not illustrated in the drawing due to the effect of an electric field formed by a voltage applied to an extraction electrode 3 and a base electrode 4c disposed opposite the sample plate 1.
More specifically, at the point in time when the sample S is irradiated with the laser beam, the same voltage VE is applied to both the sample plate 1 and the extraction electrode 3, and a prescribed base voltage VB is applied to the base electrode 4c. The base electrode 4c is typically grounded, so VB=0 in this case. As a result, the potential distribution on the ion optical axis C is as illustrated in FIG. 6(b). That is, since there is no potential gradient (meaning that there is essentially no electric field) in the extraction region between the sample plate 1 and the extraction electrode 3, the ions generated from the sample S due to laser beam irradiation are not accelerated. In this state, the sample S moves farther away (moving to the right in the drawing) when the ions have a larger initial energy at the time of ion generation, so at the point when a certain amount of time has passed after ion generation, the sample S is located closer to the extraction electrode 3 when the ions have a larger initial energy, regardless of the mass/charge ratios of the ions.
Once a certain delay time (ordinarily approximately several tens to several hundreds of nsec) has passed after laser beam irradiation, voltage applied to the sample plate 1 is increased stepwise from VE to VS. As a result, as illustrated in FIG. 6(c), an electric field having a downward-sloping potential gradient from the sample plate 1 toward the extraction electrode 3 is formed in the extraction region. Various ions that had been present in the extraction region immediately before are simultaneously accelerated by this electric field. At this time, the acceleration voltage is higher for ions at positions closer to the sample plate 1—that is, ions with a smaller initial energy—so the kinetic energy provided to the ions is large. Accordingly, ions with a smaller initial energy at the time of ion generation are fed into the flight space at a greater speed, even if the ions are of the same type, so while the ions introduced into the flight space with a delay are flying, the ions gradually catch up to preceding ions of the same type with a relatively large initial energy and ultimately reach the detector at roughly the same time. The effects of fluctuation in initial energy among ions of the same type are thus eliminated, which makes it possible to achieve high time convergence.
The above is the principle of the time convergence enhancing effect of a typical delayed extraction method used conventionally. However, such delayed extraction has the following such problems. Specifically, the correction of fluctuation in the initial energy described above is achieved by correcting the kinetic energy by changing the potential energy of each ion. The average value of the initial speed (or initial energy) of the ions generated from the sample S by laser beam irradiation is roughly constant, regardless of the mass/charge ratio. Therefore, the energy required for correction is proportional to the mass/charge ratio, and the voltage value required for correction (potential difference ΔV with VE in FIG. 6(c)) also depends on the mass/charge ratio. On the other hand, the ions are generated within a very small space near the surface of the sample S, and the electric field does not act on the extraction region during a free movement period until the voltage applied to the sample plate 1 is increased from VE to VS when delayed extraction is executed, so the spatial distribution of the ions at the time when the acceleration voltage is applied after a certain delay time has passed is unrelated to the mass/charge ratio. FIG. 8(b) is a conceptual diagram illustrating the spatial distribution of ions at this time.
In order to increase the time convergence of ions of the same type so as to enhance mass resolution, it is necessary to correct fluctuation in the initial energy appropriately, so it is necessary to apply an appropriate acceleration voltage (potential difference ΔV described above) to the ions for each mass/charge ratio. However, since the spatial distribution of the ions at the time of the application of the acceleration voltage is unrelated to the mass/charge ratio, although appropriate correction is possible for types of ions having certain mass/charge ratios when the acceleration voltage is set to a certain value, sufficient correction is not possible for types of ions having other mass charge/ratios. Therefore, the mass/charge ratio range over which the mass resolution is improved by conventional delayed extraction is limited, which leads to the problem that it is difficult to improve the mass resolution over a wide mass/charge ratio range.
Here, a MALDI ion source is used as an example of an ion source, but the same problem arises even with ion sources of other ionization methods used as TOFMS iron sources—for example, a laser desorption ionization (LDI) method that does not use a matrix, a secondary ion mass spectrometry (SIMS) method, a desorption electrospray ionization (DESI) method, a plasma desorption ionization method (PDI), or the like—configured so as to generate ions from a sample during a short period of time, extract and accelerate the ions with an electric field, and feed the ions into a flight space.